An in situ instrument for planar O2 optode measurements at benthic interfaces

A new in situ instrument for two‐dimensional mapping of oxygen in coastal sediments is presented. The measuring principle is described, and potential mechanical disturbances, solute and particle smearing associated with the measurements, and calibration routines are evaluated. The first in situ measurements obtained in two different benthic communities are presented. In a shallow photosynthetic sediment (1 m of water depth), an extensive horizontal and temporal variation in the O2 distribution caused by benthic photosynthesis and irrigating fauna was resolved. Repetitive planar optode measurements performed along a transect in central Øresund, Denmark (17 m of water depth) revealed a positive correlation between the apparent O2 penetration depths (OP) measured with a lateral distance <5.0 mm, whereas OP measured with a larger horizontal distance (up to 50 m) were not correlated. Consequently, the OP varied in patches with a characteristic size of 5.0 mm. The instrument described is a powerful new tool for in situ characterization of spatiotemporal variations in O2 distributions within benthic communities. The instrument can be adapted for use at full ocean depths, e.g., on deep‐sea landers or remote operating vehicles

The Settlement of Industrial Disputes in Great Britain

The external phosphorus (P) loading has been halved, but the P content in the water column and the area of anoxic bottoms in Baltic proper has increased during the last 30 years. This can be explained by a temporary internal source of dissolved inorganic phosphorus (DIP) that is turned on when the water above the bottom sediment becomes anoxic. A load-response model, explaining the evolution from 1980 to 2005, suggests that the average specific DIP flux from anoxic bottoms in the Baltic proper is about 2.3 g P m(-2) year(-1). This is commensurable with fluxes estimated in situ from anoxic bottoms in the open Baltic proper and from hydrographic data in the deep part of Bornholm Basin. Oxygenation of anoxic bottoms, natural or manmade, may quickly turn off the internal P source from anoxic bottoms. This new P-paradigm should have far-reaching implications for abatement of eutrophication in the Baltic proper.Funding Agencies|Swedish EPA [NV 08/302 F-255-08]</p

Predictors for discontinuation of adjuvant hormone therapy in breast cancer patients

PURPOSE: To identify predictors of discontinuation of adjuvant hormone therapy in patients with breast cancer. PATIENTS AND METHODS: We conducted a record-linkage study based on data from Stockholm-Gotland Breast Cancer Register, Swedish Prescribed Drug Register, and self-reported questionnaire. Women diagnosed with breast cancer between 2005 and 2008 in Stockholm, Sweden, were prospectively followed for 5 years until 2013, starting from their first prescription of tamoxifen or aromatase inhibitors (N = 3,395). RESULTS: Family history of ovarian cancer (hazard ratio [HR], 1.55; 95% CI, 1.19 to 2.02); younger (< 40 years; HR, 1.39; 95% CI, 1.08 to 1.78) and older (>/= 65 years; HR, 1.15; 95% CI, 1.03 to 1.28) age; higher Charlson comorbidity index (>/= 2 v 0; HR, 1.35; 95% CI, 1.03 to 1.76); and use of analgesics (HR, 1.33; 95% CI, 1.16 to 1.52), hypnotics/sedatives (HR, 1.24; 95% CI, 1.07 to 1.43), GI drugs (HR, 1.25; 95% CI, 1.08 to 1.43), and hormone replacement therapy (HR, 1.27; 95% CI, 1.08 to 1.49) were identified as baseline predictors for hormonal treatment discontinuation. Use of analgesics (HR, 1.22; 95% CI, 1.08 to 1.37), hypnotics/sedatives (HR, 1.21; 95% CI, 1.07 to 1.37), antidepressants (HR, 1.22; 95% CI, 1.06 to 1.40), or GI drugs (HR, 1.27; 95% CI, 1.13 to 1.43), and switching therapy between tamoxifen and aromatase inhibitors (HR, 1.50; 95% CI, 1.23 to 1.83) during the first year of hormonal treatment were associated with increased risk of discontinuation during the next 4 years. CONCLUSION: Predictors identified in our study can be used in developing targeted intervention to prevent adjuvant hormone therapy discontinuation and subsequently to improve breast cancer outcomes.Swedish Research CouncilSwedish Cancer SocietyFORTESwedish Society of Medical Research (SSMF)Accepte

Accuracy of SIAscopy for pigmented skin lesions encountered in primary care: development and validation of a new diagnostic algorithm.

BACKGROUND: Diagnosing pigmented skin lesions in general practice is challenging. SIAscopy has been shown to increase diagnostic accuracy for melanoma in referred populations. We aimed to develop and validate a scoring system for SIAscopic diagnosis of pigmented lesions in primary care. METHODS: This study was conducted in two consecutive settings in the UK and Australia, and occurred in three stages: 1) Development of the primary care scoring algorithm (PCSA) on a sub-set of lesions from the UK sample; 2) Validation of the PCSA on a different sub-set of lesions from the same UK sample; 3) Validation of the PCSA on a new set of lesions from an Australian primary care population. Patients presenting with a pigmented lesion were recruited from 6 general practices in the UK and 2 primary care skin cancer clinics in Australia. The following data were obtained for each lesion: clinical history; SIAscan; digital photograph; and digital dermoscopy. SIAscans were interpreted by an expert and validated against histopathology where possible, or expert clinical review of all available data for each lesion. RESULTS: A total of 858 patients with 1,211 lesions were recruited. Most lesions were benign naevi (64.8%) or seborrhoeic keratoses (22.1%); 1.2% were melanoma. The original SIAscopic diagnostic algorithm did not perform well because of the higher prevalence of seborrhoeic keratoses and haemangiomas seen in primary care. A primary care scoring algorithm (PCSA) was developed to account for this. In the UK sample the PCSA had the following characteristics for the diagnosis of 'suspicious': sensitivity 0.50 (0.18-0.81); specificity 0.84 (0.78-0.88); PPV 0.09 (0.03-0.22); NPV 0.98 (0.95-0.99). In the Australian sample the PCSA had the following characteristics for the diagnosis of 'suspicious': sensitivity 0.44 (0.32-0.58); specificity 0.95 (0.93-0.97); PPV 0.52 (0.38-0.66); NPV 0.95 (0.92-0.96). In an analysis of lesions for which histological diagnosis was available (n = 111), the PCSA had a significantly greater Area Under the Curve than the 7-point checklist for the diagnosis of melanoma (0.83; 95% CI 0.71-0.95 versus 0.61; 95% CI 0.44-0.78; p = 0.02 for difference). CONCLUSIONS: The PCSA could have a useful role in improving primary care management of pigmented skin lesions. Further work is needed to develop and validate the PCSA in other primary care populations and to evaluate the cost-effectiveness of GP management of pigmented lesions using SIAscopy.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Volumetric mammographic density: heritability and association with breast cancer susceptibility loci.

BACKGROUND: Mammographic density is a strong heritable trait, but data on its genetic component are limited to area-based and qualitative measures. We studied the heritability of volumetric mammographic density ascertained by a fully-automated method and the association with breast cancer susceptibility loci. METHODS: Heritability of volumetric mammographic density was estimated with a variance component model in a sib-pair sample (N pairs = 955) of a Swedish screening based cohort. Associations with 82 established breast cancer loci were assessed in an independent sample of the same cohort (N = 4025 unrelated women) using linear models, adjusting for age, body mass index, and menopausal status. All tests were two-sided, except for heritability analyses where one-sided tests were used. RESULTS: After multivariable adjustment, heritability estimates (standard error) for percent dense volume, absolute dense volume, and absolute nondense volume were 0.63 (0.06) and 0.43 (0.06) and 0.61 (0.06), respectively (all P < .001). Percent and absolute dense volume were associated with rs10995190 (ZNF365; P = 9.0 × 10(-6) and 8.9 × 10(-7), respectively) and rs9485372 (TAB2; P = 1.8 × 10(-5) and 1.8 × 10(-3), respectively). We also observed associations of rs9383938 (ESR1) and rs2046210 (ESR1) with the absolute dense volume (P = 2.6 × 10(-4) and 4.6 × 10(-4), respectively), and rs6001930 (MLK1) and rs17356907 (NTN4) with the absolute nondense volume (P = 6.7 × 10(-6) and 8.4 × 10(-5), respectively). CONCLUSIONS: Our results support the high heritability of mammographic density, though estimates are weaker for absolute than percent dense volume. We also demonstrate that the shared genetic component with breast cancer is not restricted to dense tissues only.This work was supported by the Swedish Research Council (grant no. 521-2011- 3187) and Swedish Cancer Society (grant no. CAN 2013/469). The KARolinska MAmmography project for risk prediction of breast cancer study was supported by Märit and Hans Rausing’s Initiative Against Breast Cancer and the Cancer and Risk Prediction Center CRisP (http://ki.se/en/meb/crisp), a Linneus Centre (Contract ID 70867902) financed by the Swedish Research Council. KH is supported by the Swedish Research Counsil (grant no. 521-2011-3205) and JL is a UNESCO-L’OREAL International Fellow.This is the accepted manuscript. The final version is available from OUP at http://dx.doi.org/10.1093/jnci/dju33

Learning a novel technique to identify possible melanomas: are Australian general practitioners better than their U.K. colleagues?

Abstract Background Spectrophotometric intracutaneous analysis (SIAscopy™) is a multispectral imaging technique that is used to identify 'suspicious' (i.e. potentially malignant) pigmented skin lesions for further investigation. The MoleMate™ system is a hand-held scanner that captures SIAscopy™ images that are then classified by the clinician using a computerized diagnostic algorithm designed for the primary health care setting. The objectives of this study were to test the effectiveness of a computer program designed to train health care workers to identify the diagnostic features of SIAscopy™ images and compare the results of a group of Australian and a group of English general practitioners (GPs). Methods Thirty GPs recruited from the Perth (Western Australia) metropolitan area completed the training program at a workshop held in March 2008. The accuracy and speed of their pre- and post-test scores were then compared with those of a group of 18 GPs (including 10 GP registrars) who completed a similar program at two workshops held in Cambridge (U.K.) in March and April, 2007. Results The median test score of the Australian GPs improved from 79.5% to 86.5% (median increase 5.5%; p < 0.001) while the median test score of the English GPs improved from 74.5% to 86.5% (median increase 9.5%; p < 0.001). The Australian GPs had significantly higher pre-test scores but there were no significant differences in post-test scores between the Australian and English GPs or between the GPs and GP registrars. There was no significant difference in scores between GPs with previous dermoscopy experience or dermatology training. Conclusion Most of the SIAscopy™ features can be learnt to a reasonable degree of accuracy with this brief computer training program. Although the Australian GPs scored higher in the pre-test, both groups had similar levels of accuracy and speed in interpreting the SIAscopy™ features after completing the program. Scores were not affected by previous dermoscopy experience or dermatology training, which suggests that the MoleMate™ system is relatively easy to learn

Exome sequencing of contralateral breast cancer identifies metastatic disease

Women with contralateral breast cancer (CBC) have significantly worse prognosis compared to women with unilateral cancer. A possible explanation of the poor prognosis of patients with CBC is that in a subset of patients, the second cancer is not a new primary tumor but a metastasis of the first cancer that has potentially obtained aggressive characteristics through selection of treatment. Exome and whole-genome sequencing of solid tumors has previously been used to investigate the clonal relationship between primary tumors and metastases in several diseases. In order to assess the relationship between the first and the second cancer, we performed exome sequencing to identify somatic mutations in both first and second cancers, and compared paired normal tissue of 25 patients with metachronous CBC. For three patients, we identified shared somatic mutations indicating a common clonal origin thereby demonstrating that the second tumor is a metastasis of the first cancer, rather than a new primary cancer. Accordingly, these patients all developed distant metastasis within 3 years of the second diagnosis, compared with 7 out of 22 patients with non-shared somatic profiles. Genomic profiling of both tumors help the clinicians distinguish between true CBCs and subsequent metastasesVetenskapsrådetForteAccepte

Complex dynamics in coevolution models with ratio-dependent functional response

We explore the complex dynamical behavior of two simple predator-prey models of biological coevolution that on the ecological level account for interspecific and intraspecific competition, as well as adaptive foraging behavior. The underlying individual-based population dynamics are based on a ratio-dependent functional response [W.M. Getz, J. Theor. Biol. 108, 623 (1984)]. Analytical results for fixed-point population sizes in some simple communities are derived and discussed. In long kinetic Monte Carlo simulations we find quite robust, approximate 1/f noise in species diversity and population sizes, as well as power-law distributions for the lifetimes of individual species and the durations of periods of relative evolutionary stasis. Adaptive foraging enhances coexistence of species and produces a metastable low-diversity phase and a stable high-diversity phase.Comment: 19 page

Protocol for the melatools skin self-monitoring trial: a phase II randomised controlled trial of an intervention for primary care patients at higher risk of melanoma.

INTRODUCTION: Melanoma is the fifth most common cancer in the UK. Incidence rates have quadrupled over the last 30 years and continue to rise, especially among younger people. As routine screening of the general population is not currently recommended in the UK, a focus on secondary prevention through early detection and prompt treatment in individuals at increased risk of melanoma could make an important contribution to improve melanoma outcomes. This paper describes the protocol for a phase II, multisite, randomised controlled trial, in the primary care setting, for patients at increased risk of melanoma. A skin self-monitoring (SSM) smartphone 'App' was used to improve symptom appraisal and encourage help seeking in primary care, thereby promoting early presentation with skin changes suspicious of melanoma. METHODS AND ANALYSIS: We aim to recruit 200 participants from general practice waiting rooms in the East of England. Eligible patients are those identified at higher melanoma risk (using a real-time risk assessment tool), without a personal history of melanoma, aged 18 to 75 years. Participants will be invited to a primary care nurse consultation, and randomised to the intervention group (standard written advice on skin cancer detection and sun protection, loading of an SSM 'App' onto the participant's smartphone and instructions on use including self-monitoring reminders) or control group (standard written advice alone). The primary outcomes are consultation rates for changes to a pigmented skin lesion, and the patient interval (time from first noticing a skin change to consultation). Secondary outcomes include patient sun protection behaviours, psychosocial outcomes, and measures of trial feasibility and acceptability. ETHICS AND DISSEMINATION: NHS ethical approval has been obtained from Cambridgeshire and Hertfordshire research ethics committee (REC reference 16/EE/0248). The findings from the MelaTools SSM Trial will be disseminated widely through peer-reviewed publications and scientific conferences. TRIAL REGISTRATION NUMBER: ISCTRN16061621.This work was supported by FMW’s Clinician Scientist award (RG 68235) from the National Institute for Health Research (NIHR). ... The paper also presents independent research funded/supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research & Care (CLAHRC) East of England, at Cambridgeshire and Peterborough NHS Foundation Trust